posted on 2022-03-09, 13:33authored byDeblina Sarkar, Monalisa Chowdhury, Prasanta Kumar Das
Supramolecular
materials that respond to external triggers are
being extensively utilized in developing spatiotemporal control in
biomedical applications ranging from drug delivery to diagnostics.
The present article describes the development of self-assembled vesicles
in 1:9 (v/v), tetrahydrofuran (THF)–water by naphthalimide-based
azo moiety containing amphiphile (NI-Azo) where azo moiety
would act as the stimuli-responsive junction. The self-assembly of NI-Azo took place through H-type of aggregation.
Microscopic and spectroscopic analyses confirmed the formation of
supramolecular vesicles with a dimension of 200–250 nm. Azo
(−NN−) moiety is known to get reduced to amine
derivatives in the presence of the azoreductase enzyme, which is overexpressed
in the hypoxic microenvironment. The absorbance intensity of this
characteristic azo (−NN−) moiety of NI-Azo (1:9 (v/v), THF–water) at 458 nm got diminished in the presence
of both extracellular and intracellular bacterial azoreductase extracted
from Escherichia coli bacteria. The
same observation was noted in the presence of sodium dithionite (mimic
of azoreductase), indicating that azoreductase/sodium dithionite induced
azo bond cleavage of NI-Azo, which was confirmed by matrix-assisted
laser desorption ionization time-of-flight spectrometric data of the
corresponding aromatic amine fragments. The anticancer drug, curcumin,
was encapsulated inside NI-Azo vesicles that successfully
killed B16F10 cells (cancer cells) in CoCl2-induced hypoxic
environment owing to the azoreductase-responsive release of drug.
The cancer cell killing efficiency by curcumin-loaded NI-Azo vesicles in the hypoxic condition was 2.15-fold higher than that
of the normoxic environment and 2.4-fold higher compared to that of
native curcumin in the hypoxic condition. Notably, cancer cell killing
efficiency of curcumin-loaded NI-Azo vesicles was 4.5-
and 1.9-fold higher than that of noncancerous NIH3T3 cells in normoxic
and hypoxic environments, respectively. Cell killing was found to
be primarily through the early apoptotic pathway.